Abstract
Copper-dependent metalloenzymes play essential roles in biology. However, unraveling how the active sites and the surrounding environment influence their functions presents a significant challenge. Inspired by Cu enzymes, we report de novo designed artificial copper proteins (ArCuPs) within trimeric (3SCC) and tetrameric (4SCC) self-assemblies, featuring a trigonal Cu(His)3 and a square pyramidal Cu(His)4(OH2) coordination. 3SCC electrocatalyzes C-H oxidation, but 4SCC does not. CuI-3SCC reacts more rapidly with H2O2 compared to O2, while 4SCC is less active. These trends mirror the peroxygenation of lytic polysaccharide monooxygenases (LPMOs) and the unreactive nature of the particulate methane monooxygenase (pMMO) CuB site. The differences in reactivity are attributed to inherent reducibility and reoxidation processes, with ET and reorganization energies (l) along with second-sphere and outer-sphere H2O-mediated H-bonding patterns providing further insights. Modulation of second/outer-sphere H-bonding without changing the primary coordination tunes the solvent l, which renders the unreactive 4SCC active for C-H peroxidation.